A variety of experimental approaches have established that the vestibular system contributes to making adjustments in the activity of thoracic and abdominal respiratory pump muscles as well as muscles that regulate the resistance of the upper airway during movement and changes in posture. However, these effects are complex, such that the physiological role of the vestibular system in regulating the movement of air in and out of the lungs is not yet clear. Specific Aim 1 of the current proposal will determine this role by examining the consequences of a bilateral labyrinthectomy on the pressure, volume, and flow rate of air exchanged during inspiration and expiration as body orientation with respect to gravity is altered. Prior experiments have also shown that some of the neurons that relay vestibular signals to respiratory motoneurons are located in the medial medullary reticular formation, but that these cells are insufficient to produce vestibulo-respiratory responses. Our anatomical studies and physiological studies by others have revealed that additional premotor respiratory neurons are located in the spinal cord. Specific Aim 2 will test the hypothesis that spinal interneurons are elements in the neuronal circuit that mediates vestibular system influences on the movement of air in and out of the lungs. Patterned contractions of respiratory muscles are additionally responsible for producing vomiting; vestibular signals trigger this motor activity during emesis associated with motion sickness. However, the neural circuit that elicits vomiting has not yet been established, although recent evidence suggests that cells in the medial medullary reticular formation are important components in this pathway. Specific Aim 3 will test the hypothesis that medial medullary reticular formation neurons coordinate the patterned discharges of respiratory muscles that underlie vomiting, including emesis associated with motion sickness. Together, these experiments should establish the particular role that labyrinthine signals serve in adjusting the activity of respiratory muscles to compensate for the effects of gravity on these muscles, the airways, and the lungs. In addition, the location and physiological characteristics of premotor neurons that mediate labyrinthine influences on respiratory motoneuron firing, both during postural alterations and emesis, will be ascertained.